Radiation therapy has been used as a clinical treatment for many types of cancers, which have varying mortality rates. Image-guided radiation therapy (IGRT) has become an indispensable method for treating many cancers. Several methods and techniques for radiation therapeutic beam delivery have been developed and performed in clinical practice and preclinical research, including methods and techniques for human and animal subjects.
Currently, real-time imaging guidance during radiation therapy is predominately achieved by using on-board kilovoltage (kV) and megavoltage (MV) X-ray imaging systems, including MV, kV planar imaging and conventional KV cone-beam computed tomography (CBCT) imaging, in a medical linear accelerator (Linac). However, there are some limitations in these conventional IGRT architectures.
Firstly, although kV- and MV-images have helped define the gross target volume (GTV) of tumors, they cannot “see” the whole clinical target volume (CTV), which includes the GTV as well as all microscopic tumor extensions and subpopulations in the neighboring tissue, due to their limited detection sensitivity of tumor cells. For treatment planning, assumptions and guesses must be made about the CTV based on clinical or pathological experience, which in turn leads to a high degree of uncertainty in the CTV.
Secondly, most tumors are subjected to shape and spatial position changes during the course of the radiotherapy. To date, radiation oncologists have dealt with this problem by extending the CTV with appropriate safety margins, which are again guesses based on clinical experience. More often than not, these safety margins include large portions of healthy tissue within the high dose volume, which often means that more healthy tissue than tumor tissue is irradiated.
Thirdly and most importantly, up until recently, radiation oncologists largely assumed that the tumor consists of homogenous cancerous tissue, and therefore a homogeneous dose distribution was delivered to the target. However, more recent research has shown that a tumor may consist of subvolumes with very different radiobiological properties, such as hypoxic areas known to be highly radio-resistant, or regions with uncontrolled cellular proliferation, which is one of the hallmarks of malignant tumors. Other important molecular processes include apoptosis, which is a major form of cell death induced by radiation, and angiogenesis, the formation of new blood vessels from pre-existing vasculature, which is an essential step in tumor progression and metastasis. The heterogeneity of these molecular profiles within a tumor region is invisible by current onboard imaging systems, thus posing the challenge of delivering inhomogeneous doses to subvolumes of tumor with different radiosensitivities.
Thus, the current model for real-time IGRT using on-board KV- and MV-imaging and conventional CBCT has significant limitations, and there is a need in the art for IGRT systems and methods that provide improvements in targeting accuracy, dose distribution, and/or clinical outcomes in cancer treatment.
For current preclinical small animal radiation therapy research, imaging guidance during radiation therapy is mainly performed by using conventional CBCT imaging systems. As mentioned above with respect to human radiation therapy, the lack of chemical and molecular imaging information of small animals for radiation guidance in the current systems place similar limitations on small animal radiation studies, which are very important to clinical practice. Therefore, improved IGRT systems and methods are needed for accurate and efficient radiation therapy treatment studies of small animals.